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FASEB J. 2012 Nov;26(11):4584-91. doi: 10.1096/fj.12-208496. Epub 2012 Aug 2.

Double Myod and Igf2 inactivation promotes brown adipose tissue development by increasing Prdm16 expression.

Author information

1
Genetics and Development Department, Institut National de Santé et de Recherche Médicale (INSERM) U567, Centre National de Recherche Scientifique (CNRS) Unité Mixte de Recherche 8104, University of Paris Descartes, Institut Cochin, Paris, France.

Abstract

Brown fat or brown adipose tissue (BAT), found in newborn mammals as small depots localized in the interscapular region, plays a prominent role in regulating thermogenesis perinatally. The physiological importance of functional BAT has been recently reasserted in human adults. Because myoblasts and adipoblasts emerge from a common mesodermal precursor, we investigated developmental determination and the reciprocal relationship between muscle and adipocyte commitment. Here we show that a mutant mouse defective for both Igf2 and Myod genes exhibits massive BAT hypertrophy compared with wild-type and single-mutant newborns. The increased adipocyte proliferation in BAT of double-mutant newborns was associated with overexpression of the brown fat-specific marker Ucp1. More strikingly, expression of the master key gene Prdm16 involved in the switch between myogenic and brown adipogenic lineages was drastically enhanced. We further demonstrate that concomitant Myod and Igf2 inactivation accelerates differentiation of a brown preadipocyte cell line and induces lipid accumulation and increased Ucp1 and Prdm16 expression. This in vitro approach brings additional support for the implication of both Myod and Igf2 in BAT development. These results provide the first in vivo evidence that a myogenic regulator together with a growth factor act simultaneously but through independent pathways to repress Prdm16, which opens potential therapeutic perspectives for human metabolic disorders.

PMID:
22859371
DOI:
10.1096/fj.12-208496
[Indexed for MEDLINE]

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